Clinical Research and Medical Affairs, US Renal Care, Inc., Plano, Texas.
Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Kidney360. 2021 Aug 27;2(10):1600-1610. doi: 10.34067/KID.0002002021. eCollection 2021 Oct 28.
Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia.
In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0-10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set.
Of 564 eligible participants randomized to receive tenapanor (=423) or sevelamer carbonate (=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (=128) or placebo (=127) during the randomized withdrawal period. In the efficacy analysis set (=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was -1.4 mg/dl (<0.0001); in the ITT analysis set (=243), the estimated mean difference was -0.7 mg/dl (=0.002). Loosened stools were the most frequently reported adverse event (53% during the randomized treatment period). Serious adverse events were reported more frequently for participants treated with sevelamer carbonate (16%-23% across the three study periods) compared with tenapanor (11%-17%).
Tenapanor reduced serum phosphate concentrations and maintained control of serum phosphate in participants receiving maintenance dialysis, with an acceptable safety and tolerability profile.
治疗高磷血症是透析治疗的一个原则。本试验评估了特立帕肽治疗高磷血症的安全性和疗效。
在这项为期 52 周的 3 期研究（NCT03427125）中，接受维持性透析且磷血症（血清磷 6.0-10.0mg/dl）且磷结合剂冲洗后增加 1.5mg/dl 的参与者被随机分为（3:1）特立帕肽 30mg 每日两次，共 26 周（随机治疗期）或碳酸钙司维拉姆（52 周安全性对照）。完成 26 周特立帕肽治疗的参与者（1:1）被重新随机分为特立帕肽或安慰剂 12 周（随机撤药期），并有资格进入 14 周安全性扩展期。在美国食品和药物管理局的指导下，主要疗效终点是随机治疗期结束时与随机撤药期结束时血清磷变化的差异，在随机治疗期期间血清磷下降≥1.2mg/dl 的参与者中（疗效分析集）。意向治疗（ITT）分析集也评估了疗效。
在随机治疗期接受特立帕肽（=423）或碳酸钙司维拉姆（=141）的 564 名符合条件的参与者中，255 名（60%）特立帕肽组随后在随机撤药期内被重新随机分为特立帕肽（=128）或安慰剂（=127）。在疗效分析集（=131）中，特立帕肽与安慰剂从随机撤药期开始到结束时血清磷水平估计平均变化的差异为-1.4mg/dl（<0.0001）；在 ITT 分析集（=243）中，估计的平均差异为-0.7mg/dl（=0.002）。在随机治疗期，最常报告的不良事件是稀便（53%）。与特立帕肽组（三个研究期间为 11%-17%）相比，碳酸钙司维拉姆组报告的严重不良事件更频繁（16%-23%）。
特立帕肽降低了接受维持性透析治疗的参与者的血清磷浓度，并维持了血清磷的控制，具有可接受的安全性和耐受性。
